The Journal of immunology : official journal of the American Association of Immunologists
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In the early stages of sepsis, lymphocytes undergo apoptosis, resulting in lymphopenia and immunosuppression. The trigger for septic lymphopenia is unknown. Using the polymicrobial model of murine sepsis, we investigated the role of C5a receptors in septic lymphopenia. ⋯ Ab-mediated neutralization of histones prevented the development of lymphopenia in sepsis. Together, these results describe a new pathway of septic lymphopenia involving complement and extracellular histones. Targeting of this pathway may have therapeutic benefit for patients with sepsis or other serious illness.
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In multiple clinical conditions, including trauma and hemorrhage, reperfusion magnifies ischemic tissue damage. Ischemia induces expression of multiple neoantigens, including lipid alterations that are recognized by the serum protein, β2-glycoprotein I (β2-GPI). During reperfusion, binding of β2-GPI by naturally occurring Abs results in an excessive inflammatory response that may lead to death. ⋯ In addition, TLR2(-/-) mice also did not express other novel Ags, suggesting a sequential response. Unlike other TLRs, TLR2(-/-) mice lacked the appropriate Ab repertoire to induce intestinal IR tissue damage or inflammation. Together, these data suggest that, in addition to the inflammatory response, IR-induced injury requires TLR2 for naturally occurring Ab production.